123 results on '"Classen S"'
Search Results
2. Perceptions of Autonomous Shuttles for Adults With Spinal Cord Injuries
- Author
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Mason, Justin, primary, Hanson, C., additional, Fox, E. J., additional, Burns, H., additional, Joseph, J., additional, Horwitz, H., additional, and Classen, S., additional
- Published
- 2023
- Full Text
- View/download PDF
3. OC-0429 Interplay of replication stress and immune signaling drives radioresistance in BRCA1 mutated cells
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Classen, S., primary, Rahlf, E., additional, Jungwirth, J., additional, Gehre, S., additional, Rückert, M., additional, Pospiech, H., additional, Rothkamm, K., additional, Gaipl, U.S., additional, Petersen, C., additional, and Borgmann, K., additional
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- 2023
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- View/download PDF
4. Author Correction: Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system
- Author
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Kaur, H., Carvalho, J., Looso, M., Singh, P., Chennupati, R., Preussner, J., Günther, S., Albarrán-Juárez, J., Tischner, D., Classen, S., Offermanns, S., and Wettschureck, N.
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- 2019
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5. Valvulotomy of the great saphenous vein in ex situ non-reversed and in situ setting: a multicenter post-market study to assess the safety and efficacy of the AndraValvulotome™".
- Author
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Souri, Yaser, Liebetrau, Dominik, Hyhlik-Dürr, Alexander, Vascular Investigators, Weigang, E., Kemke, J., Branzan, D., Wilhelmi, M., Classen, S., Pfister, K., Kuhnert, M., Seifert, S., Derwich, W., and Stavroulakis, K.
- Subjects
SAPHENOUS vein ,PERIPHERAL vascular diseases ,PULSATILE flow ,DUPLEX ultrasonography ,BLOOD flow - Abstract
Purpose: To evaluate the safety and technical success of the AndraValvulotome™ device (Andramed GmbH, Reutlingen, Germany) in patients with peripheral arterial disease (PAD) requiring bypass surgery using the great saphenous vein (GSV) as graft. Methods: This was a multicenter, post-market observational study conducted in 2021 in 11 German centers. Safety and efficacy data were prospectively collected and analyzed. Primary endpoints were the absence of device-related serious adverse events until 30 ± 7 days follow-up, the clinical efficacy of valvulotomy, which was defined as pulsatile blood flow in the bypass and the number of insufficiently destroyed vein valves. Secondary endpoints were the number of valvulotomy passages, the primary patency rate of the venous bypass (determined by a color-duplex sonography showing a normal blood flow through the bypass and absence of stenosis or occlusion), and the primary technical success defined as the absence of product-specific (serious) adverse events and clinical efficacy. Results: Fifty-nine patients were enrolled. The mean age of the patients was 71 years (46–91), and 74.6% were males. The vein material used for bypass grafting had a median length of 47.5 cm (range 20–70 cm) with a median diameter of 5.0 mm (range 3–6 mm) and 4.0 mm (range 2–6 mm) in the proximal and distal segments, respectively. The technical success rate was 96.6%. The primary patency rate was 89.9% at 30 days follow-up. The clinical efficacy was rated as very good in 81% of patients, fair in 17%, and poor in 2%. Between 1 and 5 (average 2.9) valvulotome passages were performed. One product-related serious adverse event was recorded (bypass vein dissection). Conclusion: The AndraValvulotome™ can be considered a safe and effective device to disrupt venous valves during in situ non-reversed bypass surgeries using GSV grafts in patients with PAD. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Percutaneous endovascular treatment of infrainguinal PAOD: Results of the PSI register study in 74 German vascular centers
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Behrendt, C.-A., Heidemann, F., Haustein, K., Grundmann, R. T., Debus, E. S., Balzer, K. M., Banafsche, R., Barbera, L., Baumhäkel, M., Blajan, E., Böhner, H., Breuer, P., Brune, U., Brunkwall, J., Bürger, T., Classen, S., Cöster, A., Dahl, P., Dus, E. S., Delgado, J. P., Dill, H., Eder, S., Fährenkemper, T., Feidicker, B., Forkel, J., Gahlen, J., Geier, B., Ghoi, R., Görtz, H., Gräbedünkel, J., Gunkel, W., Hader, O., Hammermüller, T., Hatzl, J., Hoffmann, J., Hofmann, M., Huberts, U., Jacobs, M., Kiechle, V., Kindermann, M., Kleemann, M., Kolka, P., Krahl, M., Krönert, T., Krupski-Berdien, G., Kuffner, H., Kuhnert, M., Lange, T., Lauff, V. K., Lesser, T., Liewald, F., Lommel, D., Naundorf, M., Nitschmann, K., Nöldeke, S., Noppeney, T., Oberhuber, A., Ockert, D. M., Orend, K.-H., Ossig, U., Petridis, C., Pflugradt, A., Quellmalz, U., Reimer, P., Remig, J., Richter, P., Riepe, G., Rümenapf, G., Schaefer, T., Schelzig, H., Schmidt, G., Schneider, M., Schofer, J., Seifert, S., Siggelkow, M., Sixt, S., Stautner, E., Stehr, A., Storck, M., Teßarek, J., Teebken, O. E., Thom, K.-D., Tigges, W. P., Voshage, G., Wagenbreth, K.-D., Walluscheck, K. P., Walter, D., Weidenhagen, R., Weis-Müller, B., Wenk, H., Wenk, M., Wiedner, M., Wilde, J., Wittstock, F. T., and PSI Collaborators
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- 2017
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7. 21166. AFECTACIÓN NEUROLÓGICA EN PACIENTES CON TÍTULOS ALTOS DE ANTICUERPOS GAD EN SUERO
- Author
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Lombardo del Toro, P., Falip Centellas, M., Jaraba Armas, S., Hernández Pérez, G., Nedkova Hristova, V., Casasnovas Pons, C., Jaumá Classen, S., González Mera, L., Gómez Llopico, R., García Serrano, L., Valín Villanueva, P., Sala i Padro, J., Angerri Nadal, M., Bea Sintes, M., Villarreal Miñano, J., and Morandeira Rego, F.
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- 2024
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8. Partial reduction in BRCA1 gene dose modulates DNA replication stress level and thereby contributes to sensitivity or resistance
- Author
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Classen, S. (Sandra), Rahlf, E. (Elena), Jungwirth, J. (Johannes), Albers, N. (Nina), Hebestreit, L. P. (Luca Philipp), Zielinski, A. (Alexandra), Poole, L. (Lena), Groth, M. (Marco), Koch, P. (Philipp), Liehr, T. (Thomas), Kankel, S. (Stefanie), Cordes, N. (Nils), Petersen, C. (Cordula), Rothkamm, K. (Kai), Pospiech, H. (Helmut), Borgmann, K. (Kerstin), Classen, S. (Sandra), Rahlf, E. (Elena), Jungwirth, J. (Johannes), Albers, N. (Nina), Hebestreit, L. P. (Luca Philipp), Zielinski, A. (Alexandra), Poole, L. (Lena), Groth, M. (Marco), Koch, P. (Philipp), Liehr, T. (Thomas), Kankel, S. (Stefanie), Cordes, N. (Nils), Petersen, C. (Cordula), Rothkamm, K. (Kai), Pospiech, H. (Helmut), and Borgmann, K. (Kerstin)
- Abstract
BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.
- Published
- 2022
9. Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance
- Author
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Classen, S., Rahlf, E., Jungwirth, J., Albers, N., Hebestreit, L., Zielinski, A., Poole, L., Groth, M., Koch, P., Liehr, T., Kankel, S., (0000-0001-5684-629X) Cordes, N., Petersen, C., Rothkamm, K., Pospiech, H., Borgmann, K., Classen, S., Rahlf, E., Jungwirth, J., Albers, N., Hebestreit, L., Zielinski, A., Poole, L., Groth, M., Koch, P., Liehr, T., Kankel, S., (0000-0001-5684-629X) Cordes, N., Petersen, C., Rothkamm, K., Pospiech, H., and Borgmann, K.
- Abstract
BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.
- Published
- 2022
10. OC-0263 Altered activation of the immune response causes radioresistance in HR-impaired breast cancer cells
- Author
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Classen, S., primary, Rahlf, E., additional, Jungwirth, J., additional, Poole, L., additional, Gehre, S., additional, Rückert, M., additional, Petersen, C., additional, Rothkamm, K., additional, Gaipl, U., additional, Pospiech, H., additional, and Borgmann, K., additional
- Published
- 2022
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11. Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system
- Author
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Kaur, H., Carvalho, J., Looso, M., Singh, P., Chennupati, R., Preussner, J., Günther, S., Albarrán-Juárez, J., Tischner, D., Classen, S., Offermanns, S., and Wettschureck, N.
- Published
- 2017
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12. PO-1931 Identifying resistance mechanisms in breast cancer in patient-derived organoids and 3D cell culture
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Classen, S., primary, Rahlf, E., additional, Petersen, C., additional, Rothkamm, K., additional, Toulany, M., additional, Cordes, N., additional, and Borgmann, K., additional
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- 2021
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13. P-079 - TRATAMIENTO MEDIANTE ULTRASONIDOS FOCALIZADOS DE ALTA INTENSIDAD COMO RESCATE TRAS LA CIRUGÍA DE ESTIMULACIÓN CEREBRAL PROFUNDA INEFECTIVA
- Author
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Serrano, M. Tardáguila, Rolan, D. Vilas, Aguiar, J.L. Muñoz, Ispierto, L., Ramo, R. Álvarez, Ahicart, G. Plans, Classen, S. Jaumà, Crespo, A. González, Cabeza, M.S. Pastor, Girón, S.A. Menéndez, Parada, L.F., and Alonso, C.J. Domínguez
- Published
- 2023
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14. PH-0234: The Adaptive Resistome in TNBC: Functional Targeting in Patient-derived Organoids and Cell Lines
- Author
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Classen, S., primary, Rahlf, E., additional, Görte, J., additional, Parplys, A.C., additional, Schumacher, U., additional, Petersen, C., additional, Rothkamm, K., additional, Toulany, M., additional, Cordes, N., additional, and Borgmann, K., additional
- Published
- 2020
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15. Crystal structure of ancestral apicomplexan lactate dehydrogenase with sulfate.
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Theobald, D.L., primary, Wirth, J.D., additional, Classen, S., additional, and Perlmutter, N., additional
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- 2020
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16. Crystal structure of ancestral apicomplexan lactate dehydrogenase in alternate dimer configuration with sulfate.
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Theobald, D.L., primary, Wirth, J.D., additional, Classen, S., additional, and Perlmutter, N., additional
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- 2020
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17. Crystal structure of ancestral apicomplexan lactate dehydrogenase with sulfate and NADH4.
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Theobald, D.L., primary, Wirth, J.D., additional, Classen, S., additional, and Perlmutter, N., additional
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- 2020
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18. Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral
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Martinez-Castrillo JC, Pena-Segura JL, Sanz-Cartagena P, Xenia Alonso, Arbelo-Gonzalez JM, Arriola-Pereda G, Coll-Bosch MD, Conejero-Casares JA, Garcia-Ribes A, Jauma-Classen S, Pagonabarraga J, Vidal-Valls J, and Garcia-Ruiz PJ
- Abstract
INTRODUCTION: Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families. AIM: To analyze and to answer different questions about the use of botulinum toxin type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.
- Published
- 2017
19. Erratum to “Endovascular Repair of Acute Uncomplicated Aortic Type B Dissection Promotes Aortic Remodelling: 1 Year Results of the ADSORB Trial” [Eur J Vasc Endovasc Surg 48 (3) (September/2014) 285–291]
- Author
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Brunkwall, J., primary, Kasprzak, P., additional, Verhoeven, E., additional, Heijmen, R., additional, Taylor, P., additional, Alric, P., additional, Canaud, L., additional, Janotta, M., additional, Raithel, D., additional, Malina, M., additional, Resch, Ti., additional, Eckstein, H.-H., additional, Ockert, S., additional, Larzon, T., additional, Carlsson, F., additional, Schumacher, H., additional, Classen, S., additional, Schaub, P., additional, Lammer, J., additional, Lönn, L., additional, Clough, R.E., additional, Rampoldi, V., additional, Trimarchi, S., additional, Fabiani, J.-N., additional, Böckler, D., additional, Kotelis, D., additional, von Tengg-Kobligk, H., additional, Mangialardi, N., additional, Ronchey, S., additional, Dialetto, G., additional, and Matoussevitch, V., additional
- Published
- 2015
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20. Carnosinase concentration and activity in CNDP1 (CTG)5 homozygous T2DM patients with and without nephropathy
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Zhang, S, primary, Pfister, F, additional, Lindner, H, additional, Albrecht, T, additional, Classen, S, additional, Kabtni, S, additional, Peters, V, additional, Klessens, C, additional, van den Born, J, additional, Navis, G, additional, Bakker, S, additional, de Heer, E, additional, Krämer, B, additional, Yard, B, additional, and Hauske, S, additional
- Published
- 2015
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21. Erratum to “Endovascular Repair of Acute Uncomplicated Aortic Type B Dissection Promotes Aortic Remodelling: 1 Year Results of the ADSORB Trial” [Eur J Vasc Endovasc Surg 48 (3) (September/2014) 285–291]
- Author
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Alric, P., Canaud, L., Janotta, M., Raithel, D., Malina, M., Resch, Ti., Eckstein, H.-H., Ockert, S., Larzon, T., Carlsson, F., Schumacher, H., Classen, S., Schaub, P., Lammer, J., Lönn, L., Clough, R.E., Rampoldi, V., Trimarchi, S., Fabiani, J.-N., Böckler, D., Kotelis, D., von Tengg-Kobligk, H., Mangialardi, N., Ronchey, S., Dialetto, G., Matoussevitch, V., Brunkwall, J., Kasprzak, P., Verhoeven, E., Heijmen, R., and Taylor, P.
- Published
- 2015
- Full Text
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22. Rater reliability to assess driving errors in a driving simulator.
- Author
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Classen, S., Yarney, A. K. A., Monahan, M., Winter, S. M., Platek, K., and Lutz, A. L.
- Subjects
- *
AUTOMOBILE driving , *AUTOMOBILE driving simulators , *RELIABILITY in engineering , *HIGHWAY research , *AUTOMOBILE drivers - Abstract
For studies relying on rater judgments of a vulnerable population, such as returning combat veterans, high consistency between primary and secondary raters is necessary. This study examined the inter-rater reliability of a primary and two secondary raters on scoring simulated driving assessments. Seven volunteer drivers were rated in two rounds (Round 1 n=4, Round 2 n=3). Driver performance was rated for two driving scenarios, a) ten-minute city/highway scenario, and b) six-minute suburban/residential scenario to measure driving errors. Based on a set 90% cut point for intra-class correlations (ICC), we examined each rated variable for each rater pairing. After round 1, secondary raters did not achieve the 90% cut point and participated in further training. Analysis of inter-rater reliability following round 2 showed improved inter-rater reliability, i.e., 99.3% for city/highway and 98% for the suburban/residential conditions. Our results suggest that by pinpointing incongruencies in raters' assessment of driving errors, strategies including problem identification, verifying driving errors via the simulator playback function, and establishing parameters for rating each error, can resolve such inconsistencies to significantly improve their inter-rater reliability. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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23. Exploring Transportation Challenges and Opportunities for Mobility-Vulnerable Populations Through the Social-Ecological Model.
- Author
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Jeghers M, Winter S, and Classen S
- Abstract
Community mobility is a vital activity of daily living. Mobility-vulnerable populations-individuals with incomes below the federal poverty threshold, minorities, individuals with disabilities, and older adults-face transit disparities. Advanced technologies (e.g., ride-sharing) may mitigate transportation inequities, but limited evidence considers mobility-vulnerable populations. Utilizing the social-ecological model, the team examined challenges and opportunities associated with transportation availability, accessibility, affordability, acceptability, and adaptability among two socioeconomic communities. Four focus groups were conducted using community-based participatory research principles. Community advisory boards informed focus group development and implementation. A thematic analysis was performed using the social-ecological model. Participants ( N = 23) experienced transportation challenges and opportunities at all levels of the social-ecological model-individual (e.g., bus availability), relationship (e.g., peer support), community (e.g., safety), and societal (e.g., social isolation). Findings indicate the importance of looking beyond individual factors and exploring relationships, community, and societal impacts on transportation use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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24. Integrating federated learning for improved counterfactual explanations in clinical decision support systems for sepsis therapy.
- Author
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Düsing C, Cimiano P, Rehberg S, Scherer C, Kaup O, Köster C, Hellmich S, Herrmann D, Meier KL, Claßen S, and Borgstedt R
- Subjects
- Humans, Artificial Intelligence, Machine Learning, Decision Support Systems, Clinical, Sepsis therapy
- Abstract
In recent years, we have witnessed both artificial intelligence obtaining remarkable results in clinical decision support systems (CDSSs) and explainable artificial intelligence (XAI) improving the interpretability of these models. In turn, this fosters the adoption by medical personnel and improves trustworthiness of CDSSs. Among others, counterfactual explanations prove to be one such XAI technique particularly suitable for the healthcare domain due to its ease of interpretation, even for less technically proficient staff. However, the generation of high-quality counterfactuals relies on generative models for guidance. Unfortunately, training such models requires a huge amount of data that is beyond the means of ordinary hospitals. In this paper, we therefore propose to use federated learning to allow multiple hospitals to jointly train such generative models while maintaining full data privacy. We demonstrate the superiority of our approach compared to locally generated counterfactuals. Moreover, we prove that generative models for counterfactual generation that are trained using federated learning in a suitable environment perform only marginally worse compared to centrally trained ones while offering the benefit of data privacy preservation. Finally, we integrate our method into a prototypical CDSS for treatment recommendation for sepsis patients, thus providing a proof of concept for real-world application as well as insights and sanity checks from clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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25. Automated Vehicles: Future Initiatives for Occupational Therapy Practitioners and Driver Rehabilitation Specialists.
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Classen S, Gelinas I, Barco P, Gibson B, Haffner E, Jeghers M, Wandenkolk I, and Devos H
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- Humans, Automobiles legislation & jurisprudence, Disabled Persons legislation & jurisprudence, Disabled Persons rehabilitation, Equipment Design, Professional Role, Automation legislation & jurisprudence, Automobile Driving legislation & jurisprudence, Occupational Therapy methods
- Abstract
This article addresses a critically important topic for the occupational therapy (OT) profession and driver rehabilitation specialists (DRS), related to the introduction and deployment of personal and public automated vehicles (AVs); and discusses the current and corresponding changing roles for these professionals. Within this commentary, we provide an overview of the relevant literature on AV regulations, policy, and legislation in North America, the various levels of AV technology, and inclusive and universal design principles to consider in AV deployment for people with disabilities. The role of the OT practitioner and DRS is described within the context of the person-environment-occupation-performance model, and within the guidelines of the Association for Driver Rehabilitation Specialists and the American Occupational Therapy Association. The article concludes with considerations for an extended clinical agenda, a new research agenda, and a call for action to OT practitioners and DRS, as well as to educators, certification bodies, professional organizations, and collaborators., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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26. A Randomized Controlled Trial on Automated Vehicle Technologies for Drivers With Parkinson's Disease.
- Author
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Classen S, Giang WCW, Rajkhan A, Zheng H, Gibson B, Patel B, Winter S, Jeghers M, Li Y, and Ramirez-Zamora A
- Abstract
Parkinson's disease (PD) negatively affects driver fitness. Few studies document the benefits of in-vehicle information systems (IVIS) and advanced-driver assistance systems (ADAS), the focus of this study, for drivers with PD. This study quantified the impact of IVIS and ADAS on the number of on-road driving errors. Drivers with PD ( N = 107) drove a vehicle equipped with IVIS and ADAS in traffic. The activation of IVIS and ADAS resulted in fewer driver errors. Specifically, adaptive cruise control reduced the number of speeding errors on the highway. Bradykinesia correlated with driving errors with deactivated systems. Memory impairments correlated with the total number of driving errors with activated systems. Impairments in executive function and visuospatial ability were associated with more errors during system deactivation. IVIS and ADAS reduced the total number of driving errors for PD drivers; ameliorated effects of individual variations; but memory declines posed a challenge while using these technologies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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27. Modeling temperature-dependent life-cycle toxicity of thiamethoxam in Chironomus riparius using a DEB-TKTD model.
- Author
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Koch J, Classen S, Gerth D, Dallmann N, Strauss T, Vaugeois M, and Galic N
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- Animals, Water Pollutants, Chemical toxicity, Life Cycle Stages drug effects, Neonicotinoids toxicity, Thiamethoxam toxicity, Chironomidae drug effects, Insecticides toxicity, Temperature, Larva drug effects
- Abstract
The neonicotinoid insecticide thiamethoxam (TMX) is widely used to protect crops against insect pests. Despite some desirable properties such as its low toxicity to birds and mammals, concerns have been raised about its toxicity to non-target arthropods, including freshwater insects like chironomids. Whereas multiple studies have investigated chronic effects of neonicotinoids in chironomid larvae at standardized laboratory conditions, a better understanding of their chronic toxicity under variable temperatures and exposure is needed for coherent extrapolation from the laboratory to the field. Here, we developed a quantitative mechanistic effect model for Chironomus riparius, to simulate the species' life history under dynamic temperatures and exposure concentrations of TMX. Laboratory experiments at four different temperatures (12, 15, 20, 23 °C) and TMX concentrations between 4 and 51 µg/L were used to calibrate the model. Observed concentration-dependent effects of TMX in C. riparius included slower growth, later emergence, and higher mortality rates with increasing concentrations. Furthermore, besides a typical accelerating effect on the organisms' growth and development, higher temperatures further increased the effects associated with TMX. With some data-informed modeling decisions, most prominently the inclusion of a size dependence that makes larger animals more sensitive to TMX, the model was parametrized to convincingly reproduce the data. Experiments at both a constant (20 °C) and a dynamically increasing temperature (15-23 °C) with pulsed exposure were used to validate the model. Finally, the model was used to simulate realistic exposure conditions using two reference exposure scenarios measured in Missouri and Nebraska, utilizing a moving time window (MTW) and either a constant temperature (20 °C) or the measured temperature profiles belonging to each respective scenario. Minimum exposure multiplication factors leading to a 10% effect (EP
10 ) in the survival at pupation, i.e., the most sensitive endpoint found in this study, were 25.67 and 21.87 for the Missouri scenario and 38.58 and 44.64 for the Nebraska scenario, when using the respective temperature assumptions. While the results illustrate that the use of real temperature scenarios does not systematically modify the EPx in the same direction (making it either more or less conservative when used as a risk indicator), the advantage of this approach is that it increases the realism and thus reduces the uncertainty associated with the model predictions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Josef Koch reports financial support and article publishing charges were provided by Syngenta. Silke Classen reports financial support was provided by Syngenta. Daniel Gerth reports financial support was provided by Syngenta. Natalie Dallmann reports financial support was provided by Syngenta. Tido Strauss reports financial support was provided by Syngenta. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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28. [Macroglossia: compressiontherapy as an alternative treatment option].
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Ilie A, Claßen S, Meier L, Brockmann K, Johanning K, Sudhoff H, and Todt I
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- Humans, Macroglossia therapy
- Abstract
Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.
- Published
- 2024
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29. USP7 Deregulation Impairs S Phase Specific DNA Repair after Irradiation in Breast Cancer Cells.
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Vogt M, Classen S, Krause AK, Peter NJ, Petersen C, Rothkamm K, Borgmann K, and Meyer F
- Abstract
The ubiquitin specific protease 7 (USP7) is a deubiquitinating enzyme with numerous substrates. Aberrant expression of USP7 is associated with tumor progression. This study aims to investigate how a deregulated USP7 expression affects chromosomal instability and prognosis of breast cancer patients in silico and radiosensitivity and DNA repair in breast cancer cells in vitro. The investigations in silico were performed using overall survival and USP7 mRNA expression data of breast cancer patients. The results showed that a high USP7 expression was associated with increased chromosomal instability and decreased overall survival. The in vitro experiments were performed in a luminal and a triple-negative breast cancer cell line. Proliferation, DNA repair, DNA replication stress, and survival after USP7 overexpression or inhibition and irradiation were analyzed. Both, USP7 inhibition and overexpression resulted in decreased cellular survival, distinct radiosensitization and an increased number of residual DNA double-strand breaks in the S phase following irradiation. RAD51 recruitment and base incorporation were decreased after USP7 inhibition plus irradiation and more single-stranded DNA was detected. The results show that deregulation of USP7 activity disrupts DNA repair in the S phase by increasing DNA replication stress and presents USP7 as a promising target to overcome the radioresistance of breast tumors.
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- 2024
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30. A 14-Day Double-Blind, Randomized, Controlled Crossover Intervention Study with Anti-Bacterial Benzyl Isothiocyanate from Nasturtium ( Tropaeolum majus ) on Human Gut Microbiome and Host Defense.
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Pfäffle SP, Herz C, Brombacher E, Proietti M, Gigl M, Hofstetter CK, Mittermeier-Kleßinger VK, Claßen S, Tran HTT, Dawid C, Kreutz C, Günther S, and Lamy E
- Subjects
- Female, Humans, Isothiocyanates pharmacology, Bacteria, Escherichia coli, Metabolome, Gastrointestinal Microbiome, Tropaeolum, Nasturtium
- Abstract
Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing their composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium ( Tropaeolum majus ) is known for its antimicrobial activity and is used for the treatment of infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question of whether a 14 d nasturtium intervention (3 g daily, N = 30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak but significant antibacterial effect against Escherichia coli . A significant increase in human beta defensin 1 as a parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did the circulating serum metabolome. On an individual level, some large changes were observed between sampling points, however. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species., Competing Interests: The study was partly supported by a grant from Repha GmbH, Langenhagen, Germany. Repha GmbH was not involved in the design, conduction, interpretation, or publishing of the results.
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- 2024
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31. An Examination of Two Diverse Communities: Residents' Transportation Behaviors, Challenges, and Opportunities.
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Jeghers M, Classen S, Manjunatha P, and Elefteriadou L
- Subjects
- Humans, Focus Groups, Transportation
- Abstract
The Smart Cities Collaborative aims to mitigate transportation challenges and inequities with new approaches and technologies (e.g., ridesharing). Therefore, assessing community transportation needs is essential. The team explored the travel behaviors, challenges, and/or opportunities among low- and high-socioeconomic status (SES) communities. Using Community-Based Participatory Research principles, four focus groups were conducted to investigate residents' behaviors and experiences with transportation availability, accessibility, affordability, acceptability, and adaptability. Focus groups were recorded, transcribed, and verified before thematic and content data analysis. Participants with low SES ( n = 11) discussed user-friendliness, uncleanliness, and bus accessibility challenges. Comparatively, the participants with high SES ( n = 12) discussed traffic congestion and parking. Both communities had concerns about safety and limited bus services and routes. Alternatively, opportunities included a convenient fixed-route shuttle. All groups stated the bus fare was affordable unless multiple fares or rideshare were needed. Findings provide valuable insight when developing equitable transportation recommendations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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32. Rater-Reliability of Assessing Driving Errors with a DriveSafety 250 Simulator.
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Jeghers M, Monahan M, Wersal J, and Classen S
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- Humans, Reproducibility of Results, Observer Variation, Occupational Therapy
- Abstract
This study aimed to establish inter-rater reliability among three raters while training new driver rehabilitation specialists to correctly identify driving errors on a DriveSafety 250 driving simulator. Five participants completed adaptation, residential and suburban, and city and highway scenarios. Intraclass correlation coefficients indicated scores between .623-.877 ( p = .003-.122) for the total driving errors recorded in the two scenario drives with rater agreement initially ranging between 7-8%. When analyzing the data for types of driving errors, the intraclass correlation coefficients ranged from .556-.973 ( p < .05) and rater agreement between 15-100%. Through proper training and strategy development, raters reached 100% consensus on all aspects of inter-rater reliability while assessing driving errors.
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- 2024
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33. Perceptions of Autonomous Shuttles for Adults With Spinal Cord Injuries.
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Mason J, Hanson C, Fox EJ, Burns H, Joseph J, Horwitz H, and Classen S
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- Adult, Humans, Spinal Cord Injuries, Transportation of Patients
- Abstract
Individuals with a spinal cord injury (SCI) have challenges using transportation. Autonomous shuttles (ASs), if accessible, may support their transportation needs. This study quantified the perceptions of AS for adults with and without SCI, before and after riding in the AS. We hypothesized that the perceptions of AS for individuals with SCI would improve, by the greatest magnitude, after riding in the AS. This mixed-method quasi-experimental design included 16 adults with SCI and 16 age-matched controls. While there were no differences between the groups, both groups reported having fewer perceived barriers to using AS after riding in the AS ( p = .025). After riding in the AS, both groups stated that the AS must be available, accessible, and affordable if they are to use AS. In conclusion, adults with SCI should experience AS if they are to accept and adopt this mode of transportation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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34. Crosstalk between immune checkpoint and DNA damage response inhibitors for radiosensitization of tumors.
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Classen S, Petersen C, and Borgmann K
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- Humans, DNA Repair, DNA Damage, Neoplasms genetics, Neoplasms radiotherapy
- Abstract
Purpose: This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors., Methods: A literature search was conducted in PubMed using the terms ("DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*") until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed., Results: Modern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here., Conclusion: The combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches., (© 2023. The Author(s).)
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- 2023
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35. Does in-vehicle automation help individuals with Parkinson's disease? A preliminary analysis.
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Giang WCW, Zheng H, Gibson B, Patel B, Ramirez-Zamora A, Winter S, Jeghers M, Li Y, and Classen S
- Abstract
Introduction: PD is a progressive neurodegenerative disorder that affects, according to the ICF, body systems (cognitive, visual, and motor), and functions (e.g., decreased executive functions, decreased visual acuity, impaired contrast sensitivity, decreased coordination)-all which impact driving performance, an instrumental activity of daily living in the domain of "Activity" and "Participation" according to the ICF. Although there is strong evidence of impaired driving performance in PD, few studies have explored the real-world benefits of in-vehicle automation technologies, such as in-vehicle information systems (IVIS) and advanced driver assistance systems (ADAS), for drivers with PD. These technologies hold potential to alleviate driving impairments, reduce errors, and improve overall performance, allowing individuals with PD to maintain their mobility and independence more safely and for longer periods. This preliminary study aimed to fill the gap in the literature by examining the impact of IVIS and ADAS on driving safety, as indicated by the number of driving errors made by people with PD in an on-road study., Methods: Forty-five adults with diagnosed PD drove a 2019 Toyota Camry equipped with IVIS and ADAS features (Toyota Safety Sense 2.0) on a route containing highway and suburban roads. Participants drove half of the route with the IVIS and ADAS systems activated and the other half with the systems deactivated., Results: The results suggest that systems that assume control of the driving task, such as adaptive cruise control, were most effective in reducing driving errors. Furthermore, individual differences in cognitive abilities, particularly memory, were significantly correlated with the total number of driving errors when the systems were deactivated, but no significant correlations were present when the systems were activated. Physical capability factors, such as rigidity and bradykinesia, were not significantly correlated with driving error., Discussion: Taken together, these results show that in-vehicle driver automation systems can benefit drivers with PD and diminish the impact of individual differences in driver cognitive ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Giang, Zheng, Gibson, Patel, Ramirez-Zamora, Winter, Jeghers, Li and Classen.)
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- 2023
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36. Simulated Driving Errors: Indicators of Real-World Driving Events in Returning Combat Veterans.
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Classen S, Wandenkolk IC, Mason J, Stetten NE, Yarney A, and Winter S
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- Humans, Accidents, Traffic prevention & control, Exercise, Automobile Driving, Occupational Therapy, Veterans
- Abstract
Motor vehicle crashes is a leading cause of death for Veterans. We quantified the efficacy of an Occupational Therapy Driving Intervention (OT-DI) and a Traffic Safety Education (TSE) intervention on real-world driving in combat Veterans. Via a randomized trial, we assessed 42 Veterans' fitness-to-drive abilities using a CDS-250 driving simulator and driving records, to determine differences in simulated driving and real-world events pre- and post-interventions. The OT-DI group (vs. TSE) had fewer over-speeding errors ( p < .001) and total number of driving errors ( p = .002) post-intervention. At Post-Test 2, the OT-DI (vs. TSE) had a reduction in real-world speeding ( p = .05). While statistically not significant, both interventions showed reductions in real-world speeding, number of violations (OT-DI: 23% and TSE: 46% decrease) and crashes (OT-DI: 25% and TSE: 50% decrease). Veterans showed early evidence of efficacy in improving their real-world fitness-to-drive abilities via an OT-DI and TSE intervention.
- Published
- 2023
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37. A monocentric, randomized, double-blind, controlled crossover trial of nasturtium ( Tropaeolum majus ) on the lipid regulator prostaglandin E 2 .
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Herz C, Frei L, Tran HTT, Claßen S, Spöttel J, Krell M, Hanschen FS, Arvandi M, Binder N, Schreiner M, Rohn S, and Lamy E
- Abstract
Scope: As prostaglandin E2 (PGE
2 ) has important roles in physiological and inflammatory functions, a double-blind randomized controlled crossover study to investigate the potential of nasturtium ( Tropaeolum majus ) for modulating PGE2 was conducted, aiming at clarifying the role of benzyl isothiocyanate (BITC). As secondary parameters leukotriene 4 (LTB4 ), and cytokine release (tumor necrosis factor alpha, TNF-α; interleukins IL-1β, IL-10, and IL-12) were quantified., Methods and Results: Thirty-four healthy female participants consumed 1.5 g nasturtium containing BITC, ( verum ) or no BITC (control) twice a day for 2 weeks each. Nasturtium intervention resulted in an increase in mean PGE2 levels in serum samples ( verum : 1.76-fold, p ≤ 0.05; control: 1.78-fold, p ≤ 0.01), and ex vivo stimulated peripheral blood mononuclear cells (PBMC) ( verum : 1.71-fold, p ≤ 0.01; control: 1.43-fold). Using a pre-to-post responder analysis approach, 18 of 34 subjects showed a > 25% PGE2 increase in serum, while it was >25% decreased for 9 subjects (stimulated PBMC: 14 and 8 of 28, respectively). Under the selected conditions, the BITC content of nasturtium did not affect the observed changes in PGE2 . Verum intervention also increased mean LTB4 serum level (1.24-fold, p ≤ 0.01), but not in LPS stimulated PBMC, and significantly increased TNF- α release in stimulated PBMC after 3 h ( verum : 1.65-fold, p = 0.0032; control: 1.22-fold, p = 0.7818). No change was seen in the anti-inflammatory cytokine IL-10, or the pro-inflammatory cytokines IL-1β, and IL-12., Conclusion: In contrast to the previously reported in vitro results, on average, LPS activated PBMC and serum from both groups showed increased PGE2 levels. Further analyses suggest that PGE2 release after intervention could possibly depend on the baseline PGE2 level. Identification of phenotypes that respond differently to the nasturtium intervention could be useful to establish personalized approaches for dosing phytopharmaceuticals medicines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herz, Frei, Tran, Claßen, Spöttel, Krell, Hanschen, Arvandi, Binder, Schreiner, Rohn and Lamy.)- Published
- 2023
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38. Public mental health during and after the SARS-CoV-2 pandemic: Opportunities for intervention via emotional self-efficacy and resilience.
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Karnaze MM, Kious BM, Feuerman LZ, Classen S, Robinson JO, Bloss CS, and McGuire AL
- Abstract
Importance: During the pandemic, the number of United States adults reporting clinically significant symptoms of anxiety and depression sky-rocketed, up from 11% in 2020 to more than 40% in 2021. Our current mental healthcare system cannot adequately accommodate the current crisis; it is therefore important to identify opportunities for public mental health interventions., Objective: Assess whether modifiable emotional factors may offer a point of intervention for the mental health crisis., Design Setting and Participants: From January 13 to 15, 2022, adults living in the United States were recruited via Amazon Mechanical Turk to complete an anonymous survey., Main Outcomes and Measures: Linear regressions tested whether the primary outcomes during the SARS-CoV-2 pandemic (depressive and anxiety symptoms, burnout) were associated with hypothesized modifiable risk factors (loneliness and need for closure) and hypothesized modifiable protective factors (the ability to perceive emotions and connect with others emotionally; emotion-regulation efficacy; and resilience, or the ability to "bounce back" after negative events)., Results: The sample included 1,323 adults (mean [SD] age 41.42 [12.52] years; 636 women [48%]), almost half of whom reported clinically significant depressive (29%) and/or anxiety (15%) symptoms. Approximately 90% of participants indicated feeling burned out at least once a year and nearly half of participants (45%) felt burned out once a week or more. In separate analyses, depressive symptoms (Model A), anxiety symptoms (Model B), and burnout (Model C) were statistically significantly associated with loneliness (βModel A, 0.38; 95% CI, 0.33-0.43; βModel B, 0.30; 95% CI, 0.26-0.36; βModel C, 0.34; 95% CI, 0.28-0.41), need for closure (βModel A, 0.09; 95% CI, 1.03-1.06; βModel B, 0.13; 95% CI, 0.97-0.17; βModel C, 0.11; 95% CI, 0.07-0.16), recent stressful life events (βModel A, 0.14; 95% CI, 0.10-0.17; βModel B, 0.14; 95% CI, 0.11-0.18; βModel C, 0.10; 95% CI, 0.06-0.15), and resilience (βModel A, -0.10; 95% CI, -0.15 to -0.05; βModel B, -0.18; 95% CI, -0.23 to -0.13; βModel C, -0.11; 95% CI, -0.17 to -0.05). In addition, depressive and anxiety symptoms were associated with emotional self-efficacy (βModel A, -0.17; 95% CI, -0.22 to -0.12; βModel B, -0.11; 95% CI, -0.17 to -0.06), and beliefs about the malleability of emotions (βModel A, -0.08; 95% CI, -0.12 to -0.03; βModel B, -0.09; 95% CI, -0.13 to -0.04). Associations between loneliness and symptoms were weaker among those with more emotional self-efficacy, more endorsement of emotion malleability beliefs, and greater resilience, in separate models. Analyses controlled for recent stressful life events, optimism, and social desirability., Conclusion and Relevance: Public mental health interventions that teach resilience in response to negative events, emotional self-efficacy, and emotion-regulation efficacy may protect against the development of depressive symptoms, anxiety, and burnout, particularly in the context of a collective trauma. Emotional self-efficacy and regulation efficacy may mitigate the association between loneliness and mental health, but loneliness prevention research is also needed to address the current mental health crisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Karnaze, Kious, Feuerman, Classen, Robinson, Bloss and McGuire.)
- Published
- 2023
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39. Visualizing and accessing correlated SAXS data sets with Similarity Maps and Simple Scattering web resources.
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Murray DT, Shin DS, Classen S, Brosey CA, and Hura GL
- Subjects
- X-Ray Diffraction, Scattering, Small Angle, Molecular Conformation, Macromolecular Substances, Proteins
- Abstract
Constructing a comprehensive understanding of macromolecular behavior from a set of correlated small angle scattering (SAS) data is aided by tools that analyze all scattering curves together. SAS experiments on biological systems can be performed on specimens that are more easily prepared, modified, and formatted relative to those of most other techniques. An X-ray SAS measurement (SAXS) can be performed in less than a milli-second in-line with treatment steps such as purification or exposure to modifiers. These capabilities are valuable since biological macromolecules (proteins, polynucleotides, lipids, and carbohydrates) change conformation or assembly under specific conditions that often define their biological role. Furthermore, mutation or post-translational modification change their behavior and provides an avenue to tailor their mechanics. Here, we describe tools to combine multiple correlated SAS measurements for analysis and review their application to biological systems. The SAXS Similarity Map (SSM) compares a set of scattering curves and quantifies the similarity between them for display as a color on a grid. Visualizing an entire correlated data set with SSMs helps identify patterns that reveal biological functions. The SSM analysis is available as a web-based tool at https://sibyls.als.lbl.gov/saxs-similarity/. To make data available and promote tool development, we have also deployed a repository of correlated SAS data sets called Simple Scattering (available at https://simplescattering.com). The correlated data sets used to demonstrate the SSM are available on the Simple Scattering website. We expect increased utilization of correlated SAS measurements to characterize the tightly controlled mechanistic properties of biological systems and fine-tune engineered macromolecules for nanotechnology-based applications., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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40. Feasibility of automated in-vehicle technologies on volunteers' driving performance.
- Author
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Classen S, Winter S, Wei J, Jeghers M, Rogers J, and Giang W
- Abstract
Background: Automated in-vehicle technologies, specifically in-vehicle information systems (IVIS) and advanced driver assistance systems (ADAS), are increasingly common in today's cars. Previous studies illustrate benefits of using IVIS and ADAS to improve safety, convenience, and comfort in healthy older drivers. However, research is sparse on the feasibility of such technologies for medically at-risk drivers, such as those with Parkinson's disease (PD)., Objective: This study enrolled healthy volunteer drivers to examine the feasibility of the procedures and measures for evaluating the effects of IVIS and ADAS on their driving performance., Methods: During this feasibility study researchers compared drives completed with and without support of IVIS and ADAS, as participants drove a 2019 Toyota Camry XLE. The test vehicle was equipped with IVIS, ADAS, cameras, a telematics system, and sensors. Participants drove the road course supervised by a Driver Rehabilitation Specialist (DRS)., Results: Overall study procedures and vehicle equipment were feasible and provided sufficient data collection for measuring the impact of IVIS and ADAS on driving performance. Data observation by the DRS combined with data captured from cameras and telematics, facilitated comparisons to increase data reliability and validity., Conclusions: Feasibility study findings informed a randomized clinical trial, examining the use of IVIS and ADAS technologies as an intervention to support drivers with Parkinson's disease., Competing Interests: This study was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research under award number 90IFRE0035. The authors have no conflicts of interest to declare.
- Published
- 2022
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41. Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance.
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Classen S, Rahlf E, Jungwirth J, Albers N, Hebestreit LP, Zielinski A, Poole L, Groth M, Koch P, Liehr T, Kankel S, Cordes N, Petersen C, Rothkamm K, Pospiech H, and Borgmann K
- Subjects
- Humans, Female, Cell Line, Tumor, BRCA1 Protein genetics, BRCA1 Protein metabolism, Homologous Recombination, DNA Repair genetics, DNA Replication, DNA Damage, Genes, BRCA1, Breast Neoplasms genetics, Breast Neoplasms drug therapy
- Abstract
BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1 . How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.
- Published
- 2022
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42. Physiological Dependency Explains Temperature Differences in Sensitivity Towards Chemical Exposure.
- Author
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Rakel K, Becker D, Bussen D, Classen S, Preuss T, Strauss T, Zenker A, and Gergs A
- Subjects
- Humans, Animals, Temperature, Neonicotinoids toxicity, Risk Assessment, Ephemeroptera, Pesticides toxicity
- Abstract
In chemical risk assessment, extrapolations from laboratory tests to more realistic conditions are essential to address the toxic effects of pesticides on individuals and populations under field conditions. To transfer toxicological laboratory tests to differing temperature conditions, or outdoor field scenarios, the consideration of temperature dependence is essential and increases realism. Special consideration is given to the impact of temperature on direct sensitivity of organisms to pesticides, for which there are only few modelling approaches available so far. We present a concept for applying physiological temperature dependencies to toxicokinetic-toxicodynamic (TKTD) parameters in the General Uniformed Threshold model of Survival (GUTS). To test this approach in an exemplary study, temperature dependencies from studies on the developmental rate of the mayfly Cloeon dipterum were applied to the parameters of a previously parameterised TKTD model of this species after exposure to imidacloprid. Using a physiologically derived temperature correction for the TKTD rate constants, model predictions for independently conducted toxicology experiments with temperature ranges between 7.8 and 26.4 °C were performed for validation. Our approach demonstrates the successful transfer of a physiological observed temperature dependency on toxicity parameters and survival patterns for Cloeon dipterum and imidacloprid as a case study., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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43. Home modifications and repurposing: perspectives on the accessibility, affordability, and attractiveness.
- Author
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Struckmeyer LR, Campbell N, Ellison C, Ahrentzen S, and Classen S
- Subjects
- Costs and Cost Analysis, Housing, Humans, Disabled Persons, Self-Help Devices
- Abstract
Purpose: Society has progressed in universal design guidelines and assistive devices for individuals with disabilities yet challenges due to affordability and attractiveness concerns remain to incorporate them into existing residences. Repurposing (i.e., replacing or adapting problematic fixtures or spaces, with others not originally intended for that purpose) may be the action to address the concerns of consumers. The purpose of this study was to elicit information on problems and solutions regarding home modifications and identify ways that consumers and professionals implement repurposing, that residents deemed accessible, affordable, and attractive., Methods: This convergent parallel design study consisted of focus groups who rated images of repurposed spaces. The focus groups included consumers with functional mobility and visual limitations ( n = 8); and professionals who devised or recommended home modifications ( n = 8). Participants reviewed three images of home modification solutions and completed a Likert-scale rating based on accessibility and attractiveness., Results: Focus group data indicated that high contrast, heights of fixtures, doors, and flooring - all pose threats to accessibility in the home. Consumers placed more value on attractiveness than professionals. Participants were aware and receptive to repurposing as a home modification technique but focused their discussion on adaptations., Conclusion: Overall, adoption and implementation of home modifications promote accessibility, but professionals need to consider individualized needs and preferences, before suggesting modifications.IMPLICATIONS FOR REHABILITATIONRepurposing existing spaces, features, and fixtures can serve as a method of home modification.Consumer home modification recommendations are perceived to be more effective when collaboratively and individually developed with professionals.Data gathered through focus groups can be valuable for informing practice and research in home modifications.
- Published
- 2022
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44. RCT protocol for driving performance in people with Parkinson's using autonomous in-vehicle technologies.
- Author
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Classen S, Li Y, Giang W, Winter S, Wei J, Patel B, Jeghers M, Gibson B, Rogers J, and Ramirez-Zamora A
- Abstract
Introduction: Driving is an essential facilitator of independence, community participation, and quality of life. Drivers with Parkinson's Disease (PD) make more driving errors and fail on-road evaluations more than healthy controls. In-vehicle technologies may mitigate PD-related driving impairments and associated driving errors. Establishing a rigorous study protocol will increase the internal validity and the transparency of the scientific work., Methods: We present a protocol to assess the efficacy of autonomous in-vehicle technologies (Level 1) on the driving performance of drivers with PD via a randomized crossover design with random allocation. Drivers with a PD diagnosis based on established clinical criteria (N = 105), referred by neurologists, are exposed to two driving conditions (technology activated or not) on a standardized road course as they drove a 2019 Toyota Camry. The researchers collected demographic, clinical, on-road data observational and kinematic, and video data to understand several primary outcome variables, i.e., number of speeding, lane maintenance, signaling, and total driving errors., Discussion: The protocol may enhance participant adherence, decrease attrition, provide early and accurate identification of eligible participants, ensure data integrity, and improve the study flow. One limitation is that the protocol may change due to unforeseen circumstances and assumptions upon implementation. A strength is that the protocol ensures the study team executes the planned research in a systematic and consistent way.Following, adapting, and refining the protocol will enhance the scientific investigation to quantify the nuances of driving among those with PD in the era of automated in-vehicle technologies., Trial Registration: ClinicalTrials.gov NCT04660500., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
- Published
- 2022
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45. Coordinated Health in Texas Elementary Schools' Campus Improvement Plans: Analysis of Regional Differences and Trends between 2016 and 2020.
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Classen S, Szeszulski J, Ranjit N, Rivas-Ponce G, and Hoelscher DM
- Subjects
- Cross-Sectional Studies, Health Policy, Nutrition Policy, Texas, Health Promotion, Schools
- Abstract
Schools signal health priorities through policies. Using a repeated cross-sectional study design, we compare the presence and strength of policies related to four topics-physical activity, nutrition, mental health, and bullying-described in elementary school Campus Improvement Plans (CIPs; also called school improvement plans) within Texas, across four Texas Public Health Regions (PHRs), and between 2016 and 2020. CIPs were collected using a multi-stage probability-based survey approach, scored using an adapted WellSAT tool, and analyzed to determine associations between PHR or year and health topic. Across 170 CIPs, bullying was the most frequently addressed topic, followed by mental health, physical activity, and nutrition. On average, schools addressed 2.7 ± 1.3 topics within their CIP; 38.2% of schools addressed all four, 26.5% addressed three, 12.4% addressed two, 15.3% addressed one, and 7.6% addressed none. CIPs in the same district had high levels of clustering (ICCs = 0.28-0.55). The mostly rural Panhandle PHR included the fewest topics in their CIPs and used the weakest policy language. Between 2016 and 2020, there was a decrease in the proportion of CIPs that addressed nutrition; the strength of language for mental health and bullying also decreased. Regional and time trends reveal opportunities for more robust school health policy interventions.
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- 2022
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46. Predicting Autonomous Shuttle Acceptance in Older Drivers Based on Technology Readiness/Use/Barriers, Life Space, Driving Habits, and Cognition.
- Author
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Classen S, Mason JR, Hwangbo SW, and Sisiopiku V
- Abstract
Shared autonomous vehicle services (i. e., automated shuttles, AS) are being deployed globally and may improve older adults (>65 years old) mobility, independence, and participation in the community. However, AS must be user friendly and provide safety benefits if older drivers are to accept and adopt this technology. Current potential barriers to their acceptance of AS include a lack of trust in the systems and hesitation to adopt emerging technology. Technology readiness, perceived ease of use, perceived barriers , and intention to use the technology, are particularly important constructs to consider in older adults' acceptance and adoption practices of AS. Likewise, person factors, i.e., age, life space mobility, driving habits , and cognition predict driving safety among older drivers. However, we are not sure if and how these factors may also predict older adults' intention to use the AS. In the current study, we examined responses from 104 older drivers ( M
age = 74.3, SDage = 5.9) who completed the Automated Vehicle User Perception Survey (AVUPS) before and after riding in an on-road automated shuttle (EasyMile EZ10). The study participants also provided information through the Technology Readiness Index, Technology Acceptance Measure, Life Space Questionnaire, Driving Habits Questionnaire, Trail-making Test Part A and Part B (TMT A and TMT B). Older drivers' age, cognitive scores (i.e., TMT B), driving habits (i.e., crashes and/or citations, exposure, and difficulty of driving) and life space (i.e., how far older adults venture from their primary dwelling) were entered into four models to predict their acceptance of AVs-operationalized according to the subscales (i.e., intention to use, perceived barriers , and well-being ) and the total acceptance score of the AVUPS. Next, a partial least squares structural equation model (PLS-SEM) elucidated the relationships between, technology readiness, perceived ease of use, barriers to AV acceptance, life space, crashes and/or citations, driving exposure, driving difficulty, cognition , and intention to use AS. The regression models indicated that neither age nor cognition (TMT B) significantly predicted older drivers' perceptions of AVs; but their self-reported driving difficulty ( p = 0.019) predicted their intention to use AVs: R2 = 6.18%, F (2,101) = 4.554, p = 0.040. Therefore, intention to use was the dependent variable in the subsequent PLS-SEM. Findings from the PLS-SEM ( R2 = 0.467) indicated the only statistically significant predictors of intention to use were technology readiness (β = 0.247, CI = 0.087-0.411) and barriers to AV acceptance (β = - 0.504, CI = 0.285-0.692) . These novel findings provide evidence suggesting that technology readiness and barriers must be better understood if older drivers are to accept and adopt AS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Classen, Mason, Hwangbo and Sisiopiku.)- Published
- 2021
- Full Text
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47. Clinical predictors of driving simulator performance in drivers with multiple sclerosis.
- Author
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Krasniuk S, Classen S, Morrow SA, Alvarez L, He W, Srinivasan S, and Monahan M
- Subjects
- Attention, Cognition, Computer Simulation, Humans, Memory, Short-Term, Automobile Driving, Multiple Sclerosis
- Abstract
Background: Drivers with multiple sclerosis (MS) may experience visual-cognitive impairment that affects their fitness to drive. Due to limitations associated with the on-road assessment, an alternative assessment that measures driving performance is warranted. Whether clinical indicators of on-road outcomes can also predict driving performance outcomes on a driving simulator are not fully understood., Objective: This study examined if deficits in immediate verbal/auditory recall (California Verbal Learning Test-Second Edition; CVLT2-IR) and/or slower divided attention (Useful Field of View™; UFOV2) predicted deficits in operational, tactical, or strategic maneuvers assessed on a driving simulator, in drivers with and without MS., Methods: Participants completed the CVLT2-IR, UFOV2, and a driving simulator assessment of operational, tactical, and strategic maneuvers., Results: Deficits in immediate verbal/auditory recall and slower divided attention predicted adjustment to stimuli errors, pertaining to tactical maneuvers only, in 36 drivers with MS (vs 20 drivers without MS; F (3, 51) = 6.1, p = 0.001, R
2 = 0.3, R a d j 2 = 0 . 2 )., Conclusion: The CVLT2-IR and UFOV2 capture the visual and verbal/auditory recall, processing speed, and divided attention required to appropriately adjust to stimuli in a simulated driving environment. Clinicians may use the CVLT2-IR and UFOV2 as precursors to driving performance deficits in drivers with MS.- Published
- 2021
- Full Text
- View/download PDF
48. Fidelity of a Traffic Safety Education Intervention for Combat Veterans.
- Author
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Winter SM, Caldwell KR, Brumback BA, Jeghers ME, and Classen S
- Subjects
- Humans, Automobile Driving, Occupational Therapy, Veterans
- Abstract
Equipoise, feasibility, and fidelity were studied for the control condition of an occupational therapy driving intervention in a randomized controlled trial. We ranked equipoise and feasibility of six traffic safety education methods and created an implementation fidelity competency checklist. Education method selection was informed using the proportion of concordant ranks analysis while literature and a peer review informed competency checklist development. A proctored-online course delivery had the highest rater agreement (equipoise = .96 [.87-1.00]; feasibility = .99 [.97-1.00]). Implementation fidelity was supported by a 19-component training and evaluation checklist. This study supports promoting the scientific rigor of the RCT via - equipoise, feasibility, and implementation fidelity.
- Published
- 2021
- Full Text
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49. A Social-Ecological Approach to Identify Facilitators and Barriers of Home Modifications.
- Author
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Ellison C, Struckmeyer L, Kazem-Zadeh M, Campbell N, Ahrentzen S, and Classen S
- Subjects
- Humans, Focus Groups
- Abstract
Aging individuals may face difficulty with independently navigating and interacting with their home environment. Evidence-based interventions promoting home modifications are needed to support aging-in-place across the lifespan. This study identified the facilitators and barriers to implementing home modifications from the perspectives of residents and professionals ( N = 16). Guided by a social-ecological model, researchers utilized directed content analysis of focus group interviews. While participants discussed facilitators and barriers mainly on the individual level, factors were presented at the relationship, community, and societal level of the model. Overall, the findings suggest a potential for targeted interventions on all levels of the model to promote adoption of home modifications.
- Published
- 2021
- Full Text
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50. Construct Validity and Test-Retest Reliability of the Automated Vehicle User Perception Survey.
- Author
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Mason J, Classen S, Wersal J, and Sisiopiku V
- Abstract
Fully automated vehicles (AVs) hold promise toward providing numerous societal benefits including reducing road fatalities. However, we are uncertain about how individuals' perceptions will influence their ability to accept and adopt AVs. The 28-item Automated Vehicle User Perception Survey (AVUPS) is a visual analog scale that was previously constructed, with established face and content validity, to assess individuals' perceptions of AVs. In this study, we examined construct validity, via exploratory factor analysis and subsequent Mokken scale analyses. Next, internal consistency was assessed via Cronbach's alpha (α) and 2-week test-retest reliability was assessed via Spearman's rho (ρ) and intraclass correlation coefficient (ICC). The Mokken scale analyses resulted in a refined 20-item AVUPS and three Mokken subscales assessing specific domains of adults' perceptions of AVs: (a) Intention to use ; (b) perceived barriers ; and (c) well-being . The Mokken scale analysis showed that all item-coefficients of homogeneity (H) exceeded 0.3, indicating that the items reflect a single latent variable. The AVUPS indicated a strong Mokken scale ( H
scale = 0.51) with excellent internal consistency (α = 0.95) and test-retest reliability (ρ = 0.76, ICC = 0.95). Similarly, the three Mokken subscales ranged from moderate to strong (range Hscale = 0.47-0.66) and had excellent internal consistency (range α = 0.84-0.94) and test-retest reliability (range ICC = 0.84-0.93). The AVUPS and three Mokken subscales of AV acceptance were validated in a moderate sample size ( N = 312) of adults living in the United States. Two-week test-retest reliability was established using a subset of Amazon Mechanical Turk participants ( N = 84). The AVUPS, or any combination of the three subscales, can be used to validly and reliably assess adults' perceptions before and after being exposed to AVs. The AVUPS can be used to quantify adults' acceptance of fully AVs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mason, Classen, Wersal and Sisiopiku.)- Published
- 2021
- Full Text
- View/download PDF
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